Good morning, everyone, and welcome to the Alumis conference call on the LUMUS phase IIB top line results. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the formal presentations. As a reminder, this call is being recorded, and the replay will be made available on the Alumis website following the conclusion of the event. I'd now like to turn the call over to John Schroer, Chief Financial Officer at Alumis. Please go ahead, John. Thank you. Good morning, and thank you for joining us today. Before we begin our formal comments, let me remind you that during today's webcast, we will be making forward-looking statements that represent the company's intentions, expectations, or beliefs concerning future events. These statements represent our views as of this date, are subject to risks and uncertainties, and should not be relied upon as representing our views as of any subsequent date in the future. With me on the call today are Martin Babler, our President and Chief Executive Officer, and Dr. Jörn Drappa, our Chief Medical Officer. Martin will open the call and then hand off to Jörn to walk through some of the data, including the pre-specified subgroup analyses. Martin will then review next steps before wrapping up the prepared remarks. Then we'll take questions. I would like now to turn the call over to Martin. Thank you, John, and thank you all for joining us. Let me start by acknowledging that the LUMUS phase II study trial did not meet the primary and secondary endpoints. This was clearly not the outcome we expected. However, this phase II trial has provided important insights and a clear path forward for envudeucitinib in type 1 interferon-driven diseases, including SLE. The LUMUS data confirmed the favorable profile that we have seen to date. In LUMUS, envudeucitinib was well-tolerated with no unexpected findings and was comparable to placebo. These data strengthen the overall safety data set we have for envudeucitinib, especially as we continue to expect our NDA submission for moderate to severe psoriasis in the fourth quarter of this year. Robust clinical responses were observed in the pre-specified subgroup of patients with high interferon gene signature, which represents approximately 60% of the patients enrolled in LUMUS. This analysis shows meaningful treatment effects across primary and key secondary efficacy endpoints. These results are consistent with the type 1 interferon target mechanism and confirm that envudeucitinib is working as designed. The subgroup of the population is an established and readily identifiable patient group and represents a large opportunity of moderate to severe SLE patients. Jörn will outline the factors we believe contributed to the overall outcome as well as the meaningful clinical benefit that we saw in the pre-specified subgroup of patients with high interferon gene signature. On this call, to simplify the lexicon, we will be abbreviating high interferon gene signature to IFNGS-high, and similarly, low interferon gene signature will be IFNGS-low. We believe that we have a clear path forward for regulatory engagement on phase III development for envudeucitinib in SLE, and we do not foresee significant changes to our overall development timeline. I'll now turn the call over to Jörn to go into more detail on the LUMUS results. Thank you, Martin. LUMUS was a phase II randomized, double-blind, placebo-controlled study that evaluated multiple doses of envudeucitinib in adults with moderately to severely active autoantibody positive SLE. The trial enrolled 408 patients who received one of three envudeucitinib doses or placebo for 48 weeks in Part A. The primary endpoint was the assessment of improvements in overall disease activity using the composite endpoint BICLA at week 48. Key secondary endpoints are listed on the slide. After week 48, patients had the option to roll over into the long-term open label extension portion of LUMUS, which is Part B. Let's now review the efficacy data. As Martin said, envudeucitinib did not achieve statistical significance with the primary endpoint in the overall population at week 48. The same was true for SRI-4 and other key secondary endpoints. With respect to safety, we were pleased to see that in LUMUS, envudeucitinib treatment was well-tolerated through week 48 with no new safety signals. Overall, incidence rates were lower on active treatment compared with placebo for treatment-emergent adverse events, serious adverse events, and adverse events of clinical interest. Notably, there were no reports of MACE, extended MACE, or malignancies in any treatment arms. We were encouraged to see that the pharmacodynamic data from LUMUS confirms that envudeucitinib worked as intended. As a TYK2 inhibitor, it blocks downstream type I interferon signaling, and here we see that in a dose-dependent manner. On the left panel, you see expression levels of SIGLEC-1, a biomarker that is exquisitely sensitive to TYK2 inhibition. On the right panel, you see a four-gene panel that measures the expression of interferon-regulated genes. By both of these measures, the top dose of 40 milligrams BID achieved strong target engagement with maximal downregulation of the type I interferon pathway. Before we go further into the LUMUS analyses, I would like to provide a little bit more context about the interferon gene signature characteristics in lupus patients, which play a key role in treatment response to type I interferon-targeted treatment. The distribution of interferon gene signature is bimodal with a natural separation into two distinct groups, high and low IGS groups. IGS high is an established patient group that represents approximately 70% of moderate to severe SLE patients, as reported in the SPOCS cohort study. As Martin mentioned, this subgroup is readily identifiable using commercially available assays. IGS high patients tend to have greater disease activity and typically respond more favorably to interferon pathway-targeted therapies with lower placebo response rates. Conversely, IFNGS-low patients respond less favorably to interferon-targeted therapies and show higher placebo response rates. Now let's look at the key factors that affected the LUMUS study outcome. The baseline demographics were generally well-balanced across groups. There were two key factors that impacted the overall study outcome as follows. The first is the proportion of patients with the interferon signature. The second is the disease activity as measured by BILAG. BILAG stands for British Isles Lupus Assessment Group, which measures how active a patient's lupus is across nine organ systems. Symptoms are graded through a letter scale where A denotes severe disease activity, B denotes moderate disease activity, and C denotes mild disease activity. First, let's talk about the interferon signature. LUMUS enrolled a lower than expected proportion of IFNGS-high patients, and therefore also a lower than expected proportion of patients with severe disease. For context, other phase II and phase III trials achieved approximately an 80/20 split between IFNGS-high and IFNGS-low patients. The Saphnelo study was closer to 60/40. As to why this occurred, one reason we hypothesize is that having more approved treatments available for SLE has reduced the pool of patients with severe disease activity that are available for clinical trials. In LUMUS, the interferon gene signature status was a stratification factor but was not a requirement for inclusion into LUMUS. The result was more IFNGS-low patients being enrolled than we had anticipated. Second, with regard to disease activity, the proportion of patients with severe disease activity, as indicated by a BILAG A, was slightly lower than the proportion of patients with moderate disease activity, as indicated by the presence of at least two BILAG Bs. Patients with IFNGS-low respond less favorably to interferon pathway-targeted therapies and also show a higher placebo response rate, and both of these turned out to be true in our study. When we analyzed the LUMUS data for the pre-specified subgroup of IFNGS-high patients, we observed clinically meaningful benefit across primary and secondary treatment measures in these patients. I will now walk you through these compelling results. On the left side of the table, you'll see the IFNGS-high subgroup, and on the right side of the table, you see the IFNGS-low subgroup. In the green rectangle, you'll observe that for the IFNGS-high patients, on all endpoints, there are robust responses with clear separation from placebo. I'll also point you to impressive results, not only on BICLA, but as well on SRI4, and the LLDAS. To achieve LLDAS, several criteria that incorporate both disease control and limitation of steroid exposure have to be satisfied. LLDAS is important because it answers the question of whether patients achieve a remission-like state of low disease activity, and it has a strong connection to long-term outcomes. Conversely, in the red rectangle, you'll see that there was no apparent clinical benefit from envudeucitinib in the IFNGS-low subgroup. These results are consistent with the TYK2 mechanism of action which primarily acts by down-modulating downstream type I interferon. On this slide in the top panel, the next slide, we show the response over time by dose in the IFNGS-high subgroup, with a clear separation from placebo shown in the yellow line as early as 24 weeks. In the bottom panel, you see the lack of response in the IFNGS-low subgroup. I'll now walk you through several slides comparing our data to published data on upacitinib and anifrolumab in IFNGS-high and IFNGS-low subgroups. The usual caveats around cross-trial comparisons, of course, apply. Starting with slide 13 for the IFNGS-high subgroup, we see overall strong response rates for BICLA and envudeucitinib compared to placebo, and also compared to upacitinib and anifrolumab as well. In contrast, this slide shows that it's much more difficult to characterize responses in the IFNGS-low subgroup. Response rates are a lot more variable with no clear patterns. The same holds true if we look at the SRI4 endpoint. There was clear separation from placebo in the IFNGS-high subgroup. In contrast, this slide shows that for SRI4, it's more difficult to characterize responses in the IFNGS-low subgroup with variable response rates and no clear pattern. Finally, on slide 17, we capture BICLA plus four key secondary endpoints, including CLASI-50 and SRI4 response, active joint count reduction, and glucocorticosteroid taper for envudeucitinib compared to anifrolumab. Again, there was clear separation from placebo on primary and these key secondary endpoints. To conclude, although LUMUS did not achieve its key objectives in the overall study population, the trial did provide us with deep insights that we can build upon moving forward and incorporate our findings into phase III development. Before I turn the call back to Martin, I would like to express our gratitude to the patients, families, and investigators whose participation made the LUMUS study possible. Martin? Thank you, Jörn. The data in the IFNGS-high patients show a clear treatment effect, which we believe defines the patient population for a potential phase III design and sizing. We are preparing for an end-of-phase II meeting with regulatory authorities and do not foresee significant changes to our original development timeline. We have some additional work to further characterize the responder population and prepare the LUMUS results for a future medical meeting. We believe that this represents a clear path forward for SLE. We have accomplished a lot this year, and we have some additional milestones that will be important for Alumis going forward as well. We have now demonstrated that envudeucitinib has opportunity to help patients with both IL-23 and type I interferon-driven diseases. We recognize that the key value drivers are psoriasis and pursuing interferon-driven diseases such as SLE. More broadly, we will continue to evaluate opportunities to maximize the value of our TYK2 portfolio for both patients and shareholders. With that, we'll take your questions. Operator? Thank you, Mr. Babler. We would now like to begin the Q&A portion of the call, so please hold for a brief moment while we poll for questions. Our first question comes from Eric Schmidt at Cantor Fitzgerald. Please go ahead, Eric. Thanks for taking my question, and sorry about the outcome here. I guess, how do you think about in a future phase III trial controlling for interferon gene signature high such that this doesn't happen again? Is there a way of instituting an assay that requires some percent of patients to be IFNGS-high, interferon gene signature IFNGS-high or some other metric that you're going to look at, and do you need to develop an assay if you're going to do that? No. The assays are commercially available. We did actually use this assay at screening and already in the LUMUS study. But, since at the time we did not have evidence that envudeucitinib would have no benefit for the negative population, we decided not to make this a requirement. That is something that now can clearly be adjusted since we have compelling evidence that there was no apparent treatment effect in the negative subgroup, while there was quite convincing efficacy indeed in the positive group. As a consequence, you can either completely focus a future study on the interferon signature high subgroup or at least cap the proportion of negative patients. We'll do further analysis to see which one of these possibilities makes more sense. It does seem pretty clear that this drug did not have a beneficial effect for the negative subpopulation. One, certainly, we would focus the future development on the population where it actually works, and that is quite consistent with our mission as a precision immunology company. Great. Thanks for the question, Eric. Our next question comes from Thomas Smith at Leerink. Please go ahead, Thomas. Hey, guys. Good morning. Thanks so much for taking our questions. A couple if I could. Just wondering if you could give a little bit more color on your expected timing here for the regulatory engagement and the next update. Is the expectation here you are thinking this would require one additional study, like one phase III study, or is there potentially a need for two phase III studies? Secondly, I was wondering if we could just get your thoughts on the dose response. It seems like the 40 mg BID performed quite well in that IFNGS-high subgroup on BICLA, but it seems like the 20 mg QD dose also performed well on some of these other secondary endpoints. Just wanted to get further thoughts on potential dose response in this study. Thanks so much. Yeah. To start with the first question, we will engage with regulators as soon as possible, hopefully by the end of this year. As you all know, the FDA's calendar tends to be quite busy towards the end of the year. But we will work expeditiously to prepare briefing materials and to request an interaction. With respect to dose response, I think we have a little bit more work to do. In this study, we used certain imputation methods, where patients who either failed to taper steroids or who had adverse events or clear evidence of no efficacy were imputed as non-responders. That can actually lead to some distortions across those groups. We will do some further detailed analysis, including the detailed dose response modeling, to get a better handle on dose response. You are right that in the slides, at first glance, it does not appear that there was a dose response for some endpoints, whereas there was for others. But I think we will reserve judgment until we have actually done this dose response modeling. Certainly, if you look at the PD, there was a very clear dose response, where there was progressively deeper inhibition of the type I interferon signature with increasing doses. But that does not immediately become apparent in the clinical outcomes. Great. Thank you for the questions, Thomas. Our next question comes from Terence Flynn at Morgan Stanley. Please go ahead, Terence. Great. Thanks for taking the questions. I guess, two for me. First, I was just wondering how you think about these data in the context of other indications that you might be considering. I know that was something that we're expecting to hear more about later this year in terms of how you guys are thinking beyond the current indication set. Then the second question, was just wondering if you'd comment on the placebo behavior in the two different subsets. It looks somewhat different. Just any theories for the differences in the placebo behavior across the two subsets. Thank you. Yeah. To start with the second question, I think that has been the consistent observation across the multiple trials, and it was already seen in the anifrolumab trial that the interferon negative subgroup, or the interferon gene signature low subgroup, had a much higher placebo response rate. If you recall the anifrolumab, the MUSE and TULIP programs, the active arms actually had relatively comparable response rates in between the signature high and signature low group, but the placebo response rates were much higher. The precise explanation for this is, I think, not completely clear. It just reflects the fact that these are probably biologically distinct populations, with the IFNGS-high population typically having more severe disease that is probably a little bit less susceptible to placebo responses than the more moderate or milder disease that the interferon gene signature negative patients have. I'm sorry, remind me of the first question. It escaped my mind. Oh, just the other indications. Oh, I believe, yes. Through the data, like other indications you might pursue, or does this change anything in terms of development plan for those indications? Thank you. I think it has strengthened our conviction that this is a rational target in type I interferon-mediated diseases, at least those patients who have a bona fide interferon signature. Certainly the results we've seen in the other subgroup, with respect to the CLASI, would strengthen my conviction that this should be working in cutaneous lupus as well, and we had previously communicated that we're considering development in Sjögren's, and we'll continue to evaluate that. Great. Thanks for the questions, Terence. Our next question comes from Derek Archila at Wells Fargo. Please go ahead, Derek. Hey, good morning, guys, and thanks for taking the questions. Maybe just to parry off of Terence's question, just in terms of the future indications like Sjögren's and CLE, is this now the strategy to enrich for interferon high patients as well for those studies to kind of enrich the population? Then, Jörn or Martin, just curious, are there any precedents supporting enriching for interferon gene signature high patients after an overall miss and any other types of indications or what precedents would you point to in terms of bringing this to the FDA to narrow down the population? Thanks. I think there's plenty of precedent for overall negative trials where convincing responses were identified in a subgroup and then subsequent trials honed in on that subgroup that seems to be more amenable to treatment with a given mechanism of action. I don't think that for the type I interferon signature, there's a precedent quite yet, but it is certainly a well-known paradigm in drug development that if you have a study in a broader population that clearly identifies a signal in a subgroup, that you can then subsequently go on to develop in the subgroup. I would expect that the FDA would look at our data and come to the same conclusion as we did, that there really did not seem to be any appreciable benefit for the interferon signature low group, and then agree with us that subsequent development in lupus and potentially in other indications as well should be focused on those patients that have the biology matching the mechanism of action. Thank you for the questions, Derek. Our next question comes from Alex Thompson at Stifel. Please go ahead, Alex. Hey, thanks for taking our questions. I wanted to follow up a little bit on imputations. Could you talk about discontinuations across arms here as well as in the pre-specified subgroup analyses and what that looked like and how they were imputed. Then secondly, what is the level of importance for the deucravacitinib phase III here in terms of further validation or sort of take two in SLE as you think about going forward and talking to the FDA? Thanks. With respect to the imputation method, our primary analysis used an imputation method that uses both a non-responder imputation and multiple imputation methods. In the event that patients dropped out because of an adverse event or because of lack of efficacy, they were imputed as non-responders. Then there was a second category of intercurrent events that related to the use of restricted or prohibited medications. If patients had to start a new medication to treat lupus, or they were unable to taper the steroids to the target level, or had to increase the steroids, they were also imputed as non-responders. Other missing values for reasons not related to either of those two categories were imputed using multiple imputation. That basically uses multiple data points for a given patient to predict what the response at the missing value would have been. That was the basic methodology. The rate of those dropouts ranged between 12% and 20% for the four dose arms. It was actually a little bit higher in the 40-milligram BID group, which helped to depress or further depress the response rates. That was one of the contributing factors. There is a lot more detailed analysis that needs to be done on this and sort of a post hoc and exploratory analysis to further characterize this. Then there was a second part to your question. Yeah. What do you think about the importance of the deucravacitinib phase III, as another validating data point ahead of meeting with FDA essentially later this year? I think it's going to be an important readout, right? At the end of the day, we expect that the TYK2, the mechanism works, and it's certainly going to be important for us to look at that data and to see what are the potential avenues of differentiation. Thanks for the questions, Alex. Our next question comes from Jeff Jones at Oppenheimer. Please go ahead, Jeff. Good morning, guys, and thanks for taking the question. I guess, as you think about the study design in phase III, is there a preference for enrolling solely the interferon-high versus limiting the enrollment? Is there anything further you can say on safety in terms of your observations here and whether that supports your view on prior testing requirements for, as you see with deucravacitinib, in the context of your psoriasis filing? Thanks. Yeah. To start with the second one, the safety profile was overall excellent. Consistently in all categories, whether we are talking about regular AEs or SAEs or AEs leading to discontinuation, the proportions of patients in the three active dose arms were actually lower than in placebo. Placebo had the highest rates of adverse events, and we did not really see anything that would raise eyebrows either, opportunistic infections, malignancies, these types of signals. We were really quite pleased with the safety profile that we have observed and do not think that anything we have observed would lead us to conclude that prior testing or screening for certain things would be required. And the first part, I am sorry, Jeff, I muted. Was just in terms of how you are thinking about using the gene signature. Oh, capping. Yeah, capping versus selecting. I think both are options, and we have not finalized the decision on that. Based on the data that I have shown you today, I think it is pretty clear that there is unlikely to be a major benefit to the interferon gene signature-negative population. In my mind, at least, my current thinking is that it makes more sense to really select the patients with the underlying disease pathology that matches the mechanism of action. But certainly that requires additional discussion and further consideration. Okay. Thanks. Thanks for the questions, Jeff. Our next question comes from Brian Skorney at Baird. Please go ahead, Brian. Hey, good morning, everyone. Thanks for taking my questions. Just when we think about moving forward in a phase III plan, how are you thinking about dosing given this data, understanding it's a new data set and there's probably a lot of review to do. But given the safety, it seems like you could even theoretically go higher. There seems to be a small difference between 20 and 40 on BICLA response, but a much bigger response on the interferon biomarker. Do you think the plan would ideally be to move forward with a 40 mg versus placebo study? Are you thinking of having a second dose in that study? Is there a rationale to go higher? Is there a substantial amount of work that would be required before putting in a higher dose into phase III? Thanks. Yeah. So based on the data that I see, I don't really think that a higher dose is likely to be required since when you look at the PD, it really does seem to max out and pretty completely suppress the interferon signature at the 40 BID dose. Ultimately, what dose to take forward in phase III is a work in progress. As I said, this is just top-line data, and we have really just begun to dig into the whole data set, and we'll need to do really detailed exposure response modeling to see how we can actually best correlate the PD effect that we have observed with the overall efficacy outcome. Part of the issue is that there was a dose response for some endpoints, but not for all of them. We'll really need to dig deeper into the data to see what could possibly account for this and then which dose actually makes the most sense to take forward. So that is still work in progress and not done yet. All right. Thanks, Jörn. Thanks for the questions, Brian. Our next question comes from Christopher Raymond at Raymond James. Please go ahead, Christopher. Hey, thanks. Just, can you guys quantify what actually qualifies as IFNGS-high? Just looking at the literature, it looks like it's two standard deviations from healthy. Is that the right cutoff? I guess just, I know this question was kind of asked in previous questions, but I think there's a relatively high correlation between IFNGS-high and skin involvement. But there must be some nuance here, because I know you guys control pretty tightly for patients with skin involvement. Just maybe talk a little bit about what you've learned now about that correlation. Thanks. Yeah. So clearly, skin involvement alone is not sufficient to predict the IFNGS-high status because all of our patients in the study had skin involvement, but only 60% ended up having the interferon signature. The cutoff varies by assay and by methodology, but it's actually usually fairly easy to set the cutoff. On this slide, I've shown you this bimodal distribution, and oftentimes you can just set a visual line in between the two peaks that constitutes the cutoff. Different commercial assays use different methodologies for this by standard deviation or some other method. But in general, the cutoff is actually fairly obvious. And then if I can ask a follow-up, actually. So your comment about how maybe the landscape has changed with more therapeutic options, just what does this mean, I guess, in terms of just clinical development in this field? It sounds relatively like the bar has been raised, and it might make things much more difficult going forward to get the right population. If you could expand on that, please. Yes. There's two factors, right? So there's patients, especially in those countries where approved therapies are readily available, including the U.S. Patients are given these therapies, and they are obviously no longer candidates for a clinical trial, and that somewhat reduces the pool of available patients. In addition to that, there's really pretty intense competition for this relatively narrow segment of the overall lupus population that is needed to identify a reliable signal in lupus patients. So we need to focus on those patients with relatively severely active disease in order to get the appropriate signal-to-noise ratio and avoid those placebo response rates, which in our trial, despite really significant efforts, have still turned out to be an issue, especially in the type I interferon-negative subgroup. I would expect that if you just hone in on the patient population with underlying interferon pathology, that you should be able to avoid some of this. Thanks. Great. Thanks for the questions, Christopher. So this concludes today's Q&A session. I will now turn it back to Martin for closing remarks. Thank you. I do want to emphasize that the hypothesis that we originally set out, which is that TYK2 actually, and the interferon pathway that TYK2 ultimately deactivates, is a viable therapeutic option. We believe that this data clearly supports that hypothesis. I want to thank you for your questions, and we really appreciate that you joined us today. We look forward to sharing additional progress and information with you for anifrolumab down the road later this year.